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标题: 吉利德使用Precision的ARCUS基因组编辑平台开发乙型肝炎疗法 [打印本页]

作者: StephenW    时间: 2018-9-13 17:47     标题: 吉利德使用Precision的ARCUS基因组编辑平台开发乙型肝炎疗法

Gilead to Develop Hepatitis B Therapies Using Precision's ARCUS Genome Editing Platform

Gilead Sciences says it will use Precision BioScience’s ARCUS genome editing platform to develop therapies targeting the in vivo elimination of hepatitis B virus, under a collaboration that could generate more than $445 million for Precision.

    Gilead Sciences will use Precision BioScience’s ARCUS genome editing platform to develop therapies targeting the in vivo elimination of hepatitis B virus (HBV) under a collaboration that could generate more than $445 million for Precision, the companies said.

    The companies cited preliminary studies at Gilead using ARCUS nucleases to target HBV covalently closed circular DNA (cccDNA) in vitro, which they said have shown “significant” activity against cccDNA and integrated HBV DNA in human hepatocytes.

    The ARCUS platform is derived from a natural genome-editing enzyme called homing endonucleases—site-specific DNA-cutting enzymes encoded in the genomes of many eukaryotic species. According to Precision, homing endonucleases have the unusual ability to precisely recognize long DNA sequences (12–40 base pairs) that are typically rare enough to occur only once in a complex genome. These nondestructive enzymes trigger gene conversion events that modify the genome in a very precise way, most frequently by the insertion of a new DNA sequence, the company said.

    ARCUS technology is based on the ARC nuclease, a fully synthetic enzyme similar to a homing endonuclease but significantly improved. ARC nucleases are small, possess unparalleled specificity, and can be customized to recognize a DNA sequence within any target gene, according to Precision.

    ARC nucleases are created using proprietary in silico and lab-based techniques designed to ensure maximum gene editing efficiency with minimum off-target activity. The nucleases can be optimized to control potency and specificity based on the analysis of cutting activity in a relevant model organism, Precision adds.

    Precision reasons—and Gilead apparently agrees—that the ability to target a single DNA break in a complex genome and achieve gene modification without random off-targeting makes homing endonucleases ideal as starting material for a therapeutic-grade genome editing technology.

    “We look forward to exploring this technology as an important component of our HBV cure research efforts,” John McHutchison, M.D., Gilead CSO and head of research and development, said in a statement.

    Added Precision CSO Derek Jantz, “This is an excellent application for our technology, which has made notable progress toward therapeutic in vivo editing in relevant models over the last year.”
    Top-Ranked Private Gene Editing Company

    Two weeks ago, Precision topped GEN’s list of private gene editing companies among the Top 10 Companies Leveraging Gene Editing, based on the company’s total capital raised of $135.65 million. Most of that capital, $110 million, was raised through a Series B round led by ArrowMark Partners, the third-largest financing among private biopharmas that garnered venture capital during the first half of 2018.

    While current HBV treatments—including Gilead’s Hepsera® (adefovir dipivoxil), Vemlidy® (tenofovir alafenamide), and Viread (tenofovir)—are designed to suppress HBV viral replication, they do not completely clear the virus, since the presence of covalently closed circular DNA (cccDNA) enables HBV replication if treatment is stopped.

    During the first half of this year, Vemlidy sales more than quadrupled to $134 million from $33 million in January–June 2017. However, Viread sales plummeted 68%, to $179 million from $560 million a year ago.

    Gilead does not break out Hepsera sales, but includes the treatment in its “Other” category, which includes the Pseudomonas aeruginosa (Pa) treatment Cayston® (aztreonam for inhalation solution), and the hepatitis C treatment Sovaldi® (sofosbuvir). Sales of Gilead’s “Other” drugs fell to $221 million from $730 million in the first half of 2017.

    Precision has agreed to primarily oversee the development, formulation, and preclinical evaluation of the investigational nucleases, while Gilead will be responsible for the clinical development and commercialization of potential therapies, the companies said. Gilead has agreed to fully fund the research and development.

    Gilead also agreed to pay Precision up to $445 million tied to achieving milestones, as well as tiered royalties that go up to the mid-teens on sales of commercial products developed through the collaboration
作者: StephenW    时间: 2018-9-13 17:47

吉利德使用Precision的ARCUS基因组编辑平台开发乙型肝炎疗法

Gilead Sciences表示,它将使用Precision BioScience的ARCUS基因组编辑平台开发针对体内消除乙型肝炎病毒的疗法,合作可为Precision产生超过4.45亿美元。

    吉利德科学公司将使用Precision BioScience的ARCUS基因组编辑平台开发针对体内消除乙型肝炎病毒(HBV)的疗法,这项合作可为Precision产生超过4.45亿美元的资金。

    这些公司引用Gilead的初步研究,使用ARCUS核酸酶在体外靶向HBV共价闭合环状DNA(cccDNA),他们表示已显示出对人肝细胞中cccDNA和整合HBV DNA的“显着”活性。

    ARCUS平台衍生自天然基因组编辑酶,称为归巢核酸内切酶 - 位点特异性DNA切割酶,编码在许多真核生物物种的基因组中。根据Precision,归巢核酸内切酶具有不同寻常的能力,能够精确识别长DNA序列(12-40个碱基对),这些序列通常很少见,只能在复杂的基因组中出现一次。这些非破坏性酶触发基因转换事件,以非常精确的方式修饰基因组,最常见的是通过插入新的DNA序列,该公司表示。

    ARCUS技术基于ARC核酸酶,一种类似于归巢核酸内切酶的完全合成酶,但显着改善。根据Precision,ARC核酸酶很小,具有无与伦比的特异性,可以定制识别任何靶基因内的DNA序列。

    ARC核酸酶是使用专有的计算机和实验室技术创建的,旨在确保最大的基因编辑效率和最小的脱靶活动。 Precision补充说,基于对相关模型生物体中切割活性的分析,可优化核酸酶以控制效力和特异性。

    精确的原因 - 吉利德显然同意 - 能够在复杂基因组中靶向单个DNA断裂并实现基因修饰而无需随机脱靶,这使得归巢核酸内切酶成为治疗级基因组编辑技术的起始材料。

    “我们期待将这项技术作为我们HBV治疗研究工作的重要组成部分,”Gilead CSO和研发主管John McHutchison博士在一份声明中说。

    添加精密CSO Derek Jantz,“这是我们技术的优秀应用,在过去一年中在相关模型中的体内编辑治疗方面取得了显着进展。”
    排名靠前的私人基因编辑公司

    两周前,根据该公司筹集的总价值为13655万美元的数据,Precision在利用基因编辑的十大公司中排名第一的GEN私人基因编辑公司名单。大部分资金,1.1亿美元,是由ArrowMark Partners领导的B轮融资筹集的,这是私人生物医院在2018年上半年获得风险投资的第三大融资。

    虽然目前的HBV治疗 - 包括Gilead的Hepsera®(阿德福韦酯),Vemlidy®(替诺福韦,aoffenamide)和Viread(替诺福韦) - 旨在抑制HBV病毒复制,但它们并不能完全清除病毒,因为存在共价封闭的圆形如果停止治疗,DNA(cccDNA)可以使HBV复制。

    在今年上半年,Vemlidy的销售额从2017年1月至6月的3300万美元增长了四倍多,达到1.34亿美元。然而,Viread的销售额从一年前的5.6亿美元下降了68%,降至1.79亿美元。

    吉利德没有公布Hepsera的销售情况,但包括“其他”类别的治疗,其中包括铜绿假单胞菌(Pa)处理Cayston®(吸入溶液的氨曲南)和丙型肝炎治疗Sovaldi®(sofosbuvir)。吉利德的“其他”药物的销售额从2017年上半年的7.3亿美元降至2.21亿美元。

    该公司表示,Precision已同意主要监督研究核酸酶的开发,配方和临床前评估,而Gilead将负责潜在疗法的临床开发和商业化。吉利德已同意为研究和开发提供全额资金。

    吉利德还同意支付Precision达到4.45亿美元与实现里程碑的关系,以及通过合作开发的商业产品销售达到十几岁的分层特许权使用费
作者: 齐欢畅    时间: 2018-9-13 20:58

利好,也算是。
吉利德公司一向都打有准备之仗,
作者: 默然10    时间: 2018-9-14 11:00

吉利德出手,一般比较靠谱吧。不见兔子不撒鹰。
作者: 齐欢畅    时间: 2018-9-14 21:34

不错,不知几期了




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